Hyperlipidemia is a symptom characterized by the abnormal elevation of lipoprotein levels in blood, particularly cholesterol levels in blood. Hyperlipidemia is known to be closely linked to diseases such as arteriosclerosis and myocardial infarction and its treatment is considered extremely important.
There are a variety of drugs available for the treatment hyperlipidemia or hypercholesterolemia. At present, HMG-CoA reductase inhibitors such as lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin and pitavastatin are most commonly used for its treatment. Of these, pitavastatin ((3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoic acid) is known to exhibit a potent HMG-CoA reductase inhibitory action and therefore be useful as an antihyperlipidemic agent (Japanese Patent No. 2569746, U.S. Pat. No. 5,102,888, EP No. 304,063).
The blood cholesterol level of patients with hyperlipidemia is lowered by the administration of an HMG-CoA reductase inhibitor. Many patients suffering from hyperlipidemia have a higher blood cholesterol level and their blood cholesterol level is not always possible to fully be lowered by the administration of an HMG-CoA reductase inhibitor. In such a case, treatment with an increased dose of an HMG-COA reductase inhibitor is not advisable from the viewpoint of safety.
On the other hand, ezetimibe ((3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone) is known as an antihyperlipidemic agent which inhibits absorption of diet-induced and bile-acid-induced cholesterol in the intestinal tract, thus lowering the blood cholesterol level by a mechanism different from that of the HMG-COA reductase inhibitor (WO95/08532).
The concomitant use of an HMG-CoA reductase inhibitor and ezetimibe was disclosed to be effective for lowering the blood cholesterol level and treatment of atherosclerosis (WO095/08532) . The blood cholesterol level lowering action by the coadministration of an HMG-CoA reductase inhibitor and ezetimibe was also reported (Metab. Clin. Exp., 50(10), 1234-1241 (2001)).
The effect brought about by the concomitant use of pitavastatin and ezetimibe on the treatment of hyperlipidemia remains to be seen, however.